cis,cis,trans-diamminedichloridobis(valproato)platinum(IV) | 1400659-04-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: cis,cis,trans-diamminedichloridobis(valproato)platinum(IV)
• 英文别名: diamminedichloridobis(valproato)platinum(IV)；(OC-6-33)-diamminedichloridobis(2-propylpentanoato)platinum(IV)；[Pt(IV)Cl₂(NH₃)₂(valproato)₂]；ctc-[Pt(NH3)2(VPA)2Cl2]；Azane;platinum(4+);2-propylpentanoate;dichloride；azane;platinum(4+);2-propylpentanoate;dichloride
• CAS: 1400659-04-2
• 化学式: C₁₆H₃₆Cl₂N₂O₄Pt
• 分子量: 586.459
• InChiKey: FRKZLILNIBHVCF-UHFFFAOYSA-J

计算性质

• 辛醇/水分配系数(LogP)：
  -3.77
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  82.3
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2,2-二-正丙基乙酰基氯 、 cis,cis,trans-[Pt(NH₃)₂Cl₂(OH)₂] 在 吡啶 作用下， 以 丙酮 为溶剂， 反应 4.0h， 以30%的产率得到cis,cis,trans-diamminedichloridobis(valproato)platinum(IV)
  参考文献：
  名称：

  Antiproliferative activity of Pt(IV)-bis(carboxylato) conjugates on malignant pleural mesothelioma cells

  摘要：

  The bifunctional Pt(IV) conjugate cis,cis,trans-diamminedichloridobis(valproato)platinum(IV), based on the cisplatin square-plane with two axial valproato (2-propylpentanoate, VPA) ligands, has been re-synthesized with a modified procedure and its biological activity was compared with that of its isomer cis,cis,trans-diamminedichloridobis(n-octanoato)platinum(IV). Both complexes showed a striking cytotoxic effect (in the micro or sub-micromolar range) on various human carcinoma cell lines (namely ovarian, colon, breast and lung cancer), and, in particular, on cells derived from malignant pleural mesothelioma. This remarkable activity is due to the action of the cisplatin metabolite only, generated by the intracellular Pt(IV)-> Pt(II) reduction, which concentration is greatly increased by the enhanced cellular accumulation of the original, highly lipophilic Pt(IV)-bis(carboxylato) complexes. The two axial VPA ligands are released in a too low concentration to act as histone deacetylase inhibitor (HDACI), as VPA works in the millimolar range, so that no synergism can be claimed. Moreover, n-octanoic acid is substantially deprived of any HDACI propensity. (C) 2013 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.jinorgbio.2013.09.003

文献信息

• [EN] Pt(IV) PRODRUGS<br/>[FR] PROMÉDICAMENTS PT(V)
  申请人：YISSUM RES DEV CO

  公开号：WO2017115372A1

  公开（公告）日：2017-07-06

  The invention provides a novel class of Pt-based anticancer compounds exhibiting multiple anticancer activity.

  这项发明提供了一类新型的基于铂的抗癌化合物，具有多重抗癌活性。
• An unsymmetric cisplatin-based Pt(<scp>iv</scp>) derivative containing 2-(2-propynyl)octanoate: a very efficient multi-action antitumor prodrug candidate
  作者：Elisabetta Gabano、Mauro Ravera、Ilaria Zanellato、Stefano Tinello、Andrea Gallina、Beatrice Rangone、Valentina Gandin、Cristina Marzano、Maria Grazia Bottone、Domenico Osella

  DOI：10.1039/c7dt02928d

  日期：——

  biological properties of a Pt(IV) complex containing the very active inhibitor of histone deacetylase (2-propynyl)octanoic acid, POA, as an axial ligand are reported here. The title complex, namely (OC-6-44)-acetatodiamminedichlorido(2-(2-propynyl)octanoato)platinum(IV), 1, containing POA in racemic or in enantiomeric forms, was one/two orders of magnitude more active than cisplatin, depending on the chemo-sensitivity

  此处报道了一种Pt（IV）配合物的设计，合成，表征和生物学性质，该配合物包含非常活泼的组蛋白脱乙酰基酶（2-丙炔基）辛酸POA作为轴向配体。含有外消旋或对映体形式的POA的标题复合物（OC -6-44）-乙酰氨基二氯二氯基（2-（2-丙炔基）辛基氨基）铂（IV）1比活性高一到两个数量级。顺铂，取决于癌细胞系的化学敏感性。此外，1具有比（OC -6-33）-二氨二氯双（2-丙基戊基）铂（IV）相似或什至更好的抗增殖活性，2含有两个分子的著名的组蛋白脱乙酰基酶抑制剂2-丙基戊酸（丙戊酸）。的高效力1可能是由于其高的细胞累积和DNA损伤性顺铂和组蛋白脱乙酰酶抑制剂POA，二者在细胞内减少的释放之间协同作用1。与对照组相比，口服前药1在实体瘤（鼠Lewis Lewis肺癌）模型中引起肿瘤肿块显着减少（94％），而（腹膜内）顺铂诱导的肿瘤消退为75 ％ 只要。一个很好的积累1在肿瘤块中观察到。体重的